Department of Epidemiology, Department of Clinical Medicine, Aarhus University Hospital, Aarhus University, Aarhus, Denmark.
Department of Clinical Pharmacology, Odense University Hospital, Odense, Denmark.
Cancer Chemother Pharmacol. 2023 Feb;91(2):157-165. doi: 10.1007/s00280-022-04499-z. Epub 2023 Jan 4.
Breast cancer treatment is associated with adverse effects, which may delay return-to-work. Single nucleotide polymorphisms (SNPs) may influence the risk and severity of treatment toxicities, which in turn could delay return-to-work. We examined the association of 26 SNPs with return-to-work in premenopausal women with breast cancer.
Using Danish registries, we identified premenopausal women diagnosed with non-distant metastatic breast cancer during 2007‒2011, assigned adjuvant combination chemotherapy including cyclophosphamide and docetaxel. We genotyped 26 SNPs in 20 genes (ABCB1, ABCC2, ABCG2, CYP1A1, CYP1B1, CYP3A, CYP3A4, CYP3A5, GSTP1, SLCO1B1, SLCO1B3, ARHGEF10, EPHA4, EPHA5, EPHA6, EPHA8, ERCC1, ERCC2, FGD4 and TRPV1) using TaqMan assays. We computed the cumulative incidence of return-to-work (defined as 4 consecutive weeks of work) up to 10 years after surgery, treating death and retirement as competing events and fitted cause-specific Cox regression models to estimate crude hazard ratios (HRs) and 95% confidence intervals (CIs) of return-to-work. We also examined stable labor market attachment (defined as 12 consecutive weeks of work).
We included 1,964 women. No associations were found for 25 SNPs. The cumulative incidence of return-to-work varied by CYP3A5 rs776746 genotype. From 6 months to 10 years after surgery, return-to-work increased from 25 to 94% in wildtypes (n = 1600), from 17 to 94% in heterozygotes (n = 249), and from 7 to 82% in homozygotes (n = 15). The HR showed delayed return-to-work in CYP3A5 rs776746 homozygotes throughout follow-up (0.48, 95% CI 0.26, 0.86), compared with wildtypes. Estimates were similar for stable labor market attachment.
Overall, the SNPs examined in the study did not influence return-to-work or stable labor market attachment after breast cancer in premenopausal women. Our findings did suggest that the outcomes were delayed in homozygote carriers of CYP3A5 rs776746, though the number of homozygotes was low.
乳腺癌治疗会产生不良反应，这可能会导致患者延迟重返工作岗位。单核苷酸多态性（SNP）可能会影响治疗毒性的风险和严重程度，进而导致患者延迟重返工作岗位。我们研究了 26 个 SNP 与接受包括环磷酰胺和多西紫杉醇在内的辅助联合化疗的绝经前乳腺癌女性的重返工作岗位之间的关联。
我们使用丹麦登记处，确定了 2007 年至 2011 年期间被诊断为非远处转移性乳腺癌的绝经前女性，并接受了辅助联合化疗。我们使用 TaqMan 检测方法对 20 个基因（ABCB1、ABCC2、ABCG2、CYP1A1、CYP1B1、CYP3A、CYP3A4、CYP3A5、GSTP1、SLCO1B1、SLCO1B3、ARHGEF10、EPHA4、EPHA5、EPHA6、EPHA8、ERCC1、ERCC2、FGD4 和 TRPV1）中的 26 个 SNP 进行了基因分型。我们计算了手术后 10 年内重返工作岗位（定义为连续 4 周工作）的累积发病率，将死亡和退休视为竞争事件，并使用特定于原因的 Cox 回归模型来估计重返工作岗位的粗危险比（HR）和 95%置信区间（CI）。我们还检查了稳定的劳动力市场联系（定义为连续 12 周工作）。
我们纳入了 1964 名女性。25 个 SNP 均未发现关联。CYP3A5 rs776746 基因型与重返工作岗位的累积发病率有关。手术后 6 个月至 10 年，野生型（n=1600）的重返工作岗位率从 25%增加到 94%，杂合子（n=249）从 17%增加到 94%，纯合子（n=15）从 7%增加到 82%。与野生型相比，CYP3A5 rs776746 纯合子的 HR 显示出在整个随访过程中重返工作岗位的时间延迟（0.48，95%CI 0.26，0.86）。对于稳定的劳动力市场联系，估计值相似。
总体而言，在绝经前女性的乳腺癌治疗后，研究中检测到的 SNP 并未影响重返工作岗位或稳定的劳动力市场联系。我们的研究结果表明，CYP3A5 rs776746 纯合子携带者的结果延迟，但纯合子的数量较少。
